Guenzel Adam J, DeBarber Andrea, Raymond Kimiyo, Dhamija Radhika
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA.
Department of Chemical Physiology and Biochemistry Oregon Health and Science University Portland Oregon USA.
JIMD Rep. 2021 Jan 8;59(1):3-9. doi: 10.1002/jmd2.12197. eCollection 2021 May.
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by pathogenic variants in the gene encoding the mitochondrial enzyme sterol 27-hydroxylase. Patients with CTX can present with a wide range of symptoms, but most often have evidence of tendon xanthomas along with possible cataracts, atherosclerosis, or neurological dysfunction. Regardless of clinical phenotype, CTX patients typically exhibit levels of cholestanol and bile acid precursors in the circulation that are many fold increased over normal control concentrations. Here we report two siblings, one with the rare spinal xanthomatosis phenotype and the other with a very mild form of CTX manifesting as minor tendon xanthomatosis and gastrointestinal complaints who both carry compound heterozygous variants in : NM_000784.3: c.410G > A (p.Arg137Gln) and c.1183C > T (p.Arg395Cys). However, biochemical analysis of these patients revealed normal levels of serum cholestanol and relatively mild elevations of the bile acid precursors 7α-hydroxy-4-cholesten-3-one and 7α,12α-dihydroxy-4-cholesten-3-one. The atypical biochemical presentation of these cases represents a diagnostic challenge for a disorder once thought to have a sensitive biomarker in cholestanol and highlight the need for thorough investigation of patients with symptomatology consistent with CTX that includes bile acid precursor biochemical testing and molecular analysis.
脑腱黄瘤病（CTX）是一种罕见的常染色体隐性胆汁酸合成障碍疾病，由编码线粒体酶固醇27 - 羟化酶的基因突变引起。CTX患者可出现多种症状，但最常见的是有肌腱黄瘤，同时可能伴有白内障、动脉粥样硬化或神经功能障碍。无论临床表型如何，CTX患者循环中的胆甾烷醇和胆汁酸前体水平通常比正常对照浓度高出许多倍。在此，我们报告一对兄弟姐妹，其中一人患有罕见的脊柱黄瘤病表型，另一人患有非常轻微的CTX形式，表现为轻微的肌腱黄瘤和胃肠道不适，他们均携带复合杂合变异：NM_000784.3: c.410G＞A（p.Arg137Gln）和c.1183C＞T（p.Arg395Cys）。然而，对这些患者的生化分析显示血清胆甾烷醇水平正常，胆汁酸前体7α - 羟基 - 4 - 胆甾烯 - 3 - 酮和7α,12α - 二羟基 - 4 - 胆甾烯 - 3 - 酮仅有相对轻微的升高。这些病例的非典型生化表现对一种曾被认为在胆甾烷醇中有敏感生物标志物的疾病构成了诊断挑战，并凸显了对有与CTX相符症状的患者进行全面调查的必要性，这包括胆汁酸前体生化检测和分子分析。
